The primary function of ACTH in a normal adrenal gland is the maintenance of adrenal structure and regulation of steroidogenesis. A common feature of all neoplasias is a loss of regulation of growth and in more steroid-secreting adrenocortical tumors there is an additional abnormality which is manifested in the lack of regulation of corticosteroidogenesis by ACTH. We are attempting to elucidate the basic mechanisms leading to these two defects. Towards this aim, we have identified the existence of two unique autonomous systems in the adrenocortical carcinoma that are apparently not expressed (or minimally expressed) in the normal adrenocortical cell. One is an autophosphorylating protein kinase, AUT-PK 500, and the other is an epinephrine-sensitive alpha2-adrenergic receptor. AUT-PK 500 has been purified to homogeneity and an immunoglobulin against the protein has been produced. In the fiscal year of the grant period, we will: (1)\assess the relationship of AUT-PK 500 with neoplasia; and (2)\purify and characterize alpha2-adrenergic receptors. (D)